JPS6351136B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing racemized cyclopropanecarboxylic acid derivatives, and more specifically, the present invention relates to a method for producing racemized cyclopropanecarboxylic acid derivatives, and more specifically, [In the formula, R ₁ and R ₂ each represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or an alkylene group having 3 to 5 carbon atoms by bonding R ₁ and R ₂ at the terminals. ] By reacting an anhydride of optically active cyclopropanecarboxylic acid shown with a Lewis acid to racemize it to obtain the acid anhydride, or by subsequently hydrolyzing it to obtain it as a carboxylic acid. The present invention relates to a method for producing a racemized cyclopropanecarboxylic acid derivative. The present invention also provides the general formula () [In the formula, R ₁ and R ₂ have the same meanings as above. ] Racemized cyclopropanecarboxylic acid is produced by introducing the optically active cyclopropanecarboxylic acid represented by the formula () into an anhydride of the optically active cyclopropanecarboxylic acid represented by the general formula (), and then treating in the same manner as above. A method for producing an acid derivative is provided. Among the carboxylic acids represented by the general formula (), 2,2-dimethyl-3-(2-methyl-
1-Propenyl) cyclopropane-1-carboxylic acid is called Daiichichrysanthemum acid and is a compound of esters that are well known as pyrethroid insecticides such as pyrethrin, allethrin, and phthalthrin, which are useful as low-toxicity and fast-acting insecticides. It constitutes the acid component. Also, 2,2-dimethyl-3-vinyl-cyclopropanecarboxylic acid, 2,2-dimethyl-3-cyclopentylidenemethyl-cyclopropane-1-
Carboxylic acids such as carboxylic acid and 2,2-dimethyl-3-cyclohexylidene-cyclopropane-1-carboxylic acid are also known as acid components of pyrethroid insecticides. Cyclopropanecarboxylic acid represented by the above general formula () has cis and trans geometric isomers, and each of them has (+) and (-) optical isomers, so there are a total of 4 types of isomers. exists. Generally, among these isomers, esters consisting of the trans isomer exhibit stronger insecticidal activity than the corresponding esters consisting of the cis isomer;
It is known that the esters in the ``-'' form exhibit much higher activity than the corresponding esters in the (-) form. Cyclopropanecarboxylic acid represented by the above general formula () is synthesized as a racemic mixture of cis and trans forms, that is, a (±) form, using an optically active organic base. By splitting, the (+) form is obtained, which is used to produce more highly active insecticidal compounds. The remaining (-) form optically resolved here has almost no activity as an ester, and therefore this useless (-) form can be efficiently racemized and used as a raw material for the above optical resolution. This poses a major challenge, especially when producing (+) bodies on an industrial scale. As mentioned above, the cyclopropanecarboxylic acid represented by the general formula () has two asymmetric carbon atoms at the C ₁ and C ₃ positions, so racemization is extremely difficult. Of the asymmetric carbons at the _C1 and _C3 positions, converting the configuration of only the asymmetric carbon at the _C1 position (epiformization) is relatively easier than racemization, and this method is is a method for obtaining trans-dairy chrysanthemum acid by heating the lower alkyl ester of cis-dairy chrysanthemum acid in the presence of a special basic catalyst (Special Publication No. 53).
-18495, Japanese Patent Publication No. 53-18496), or a method of heating cis-pyretholic acid chloride at high temperature (Japanese Patent Publication No. 46-24694). These methods are epimerization of the asymmetric carbon at the C _1- position, and are not methods for racemization by changing the configuration of the two asymmetric carbons at the C _1- and C ₃ -positions. On the _other hand _, some studies have been conducted on racemization methods. and reacting this with an alkali metal alcoholate in the presence of a solvent (Japanese Patent Publication No. 39-15977), or by irradiating (-)trans-dairylic acid with ultraviolet rays in the presence of a photosensitizer. Method (Special Publication No. 47-30697)
However, the former requires many reaction steps, and the latter has an inferior reaction rate, high power consumption of the light source, and a relatively short lifespan of the light source, making it difficult to implement industrially. It has various problems. Under these circumstances, the present inventors conducted various studies on the racemization of the cyclopropanecarboxylic acid derivative, and first determined that optically active cyclopropanecarboxylic acid was used as a halide, and a Lewis acid was allowed to act on this as a catalyst. discovered a racemization method using
Publication No.). As a result of further research by the present inventors,
It was discovered that racemization proceeds very favorably by allowing a Lewis acid to act on the anhydride of optically active cyclopropanecarboxylic acid represented by the general formula ().
The present inventors have found that the present invention can be applied to the racemization of optically active cyclopropanecarboxylic acid represented by the following formula, and have completed the present invention by conducting various studies. The method of the present invention will be explained below. The acid anhydride represented by the general formula () can be obtained by directly dehydrating the carboxylic acid represented by the general formula () in the presence of acetic anhydride, acetyl chloride, etc.
It can be easily obtained by a method in which a carboxylic acid halide is reacted with a carboxylic acid salt, or a method in which a carboxylic acid and an acid halide are dehydrohalogenated in the presence of a base. The acid anhydride obtained in this way contains a Lewis acid,
For example, by contacting with iodine, tin tetrachloride, iron chloride, aluminum chloride, aluminum bromide, titanium chloride, zinc chloride, or complexes thereof, racemization easily proceeds regardless of external pressure.
Among these Lewis acids, iodine gives more favorable results. The optically active carboxylic acid as a raw material may be one of the four isomers or a mixture of these in any proportion, and any degree of optical purity may be used. It goes without saying that its significance is exhibited when using a (-)-isomer or a carboxylic acid rich in (-)-isomers considering the purpose. In addition, when carrying out the reaction, it is preferable to use a solvent that does not essentially inhibit the racemization reaction, and examples of the solvent include ethers, aromatic hydrocarbons and their halides, hydrocarbons and their halides, etc. can. The amount of Lewis acid used is 1/1000 to 1/2 mole, preferably 1/200 to 1/5 per mole of the acid anhydride to be treated.
It is in the molar range. The reaction temperature is generally arbitrary within the range of -50°C to the boiling point of the acid anhydride (if a solvent is used, the boiling point of the solvent), but preferably in the range of -20°C to 150°C. The time required for the reaction may vary depending on the amount of Lewis acid used and the reaction temperature, but usually 10 minutes to 20 hours is sufficient to achieve the purpose. The racemized carboxylic acid anhydride obtained as described above can be directly reacted with a group of pyrethroid alcohols such as pyrethrolone and allethrone to lead to an insecticidal ester. It can also be reacted with a halogenating agent such as thionyl chloride to form a carboxylic acid halide, followed by reaction with the alcohols mentioned above to lead to similar insecticidal esters. In addition, racemized carboxylic acid can be easily obtained by hydrolyzing the carboxylic anhydride by adding an alkaline aqueous solution according to a conventional method, and the (+) form of the carboxylic acid can be obtained by the above-mentioned optical resolution. ,
Alternatively, it can be used as a raw material in the production of insecticidal esters. As detailed above, by the method of the present invention, the (-) form of cyclopropane carboxylic acid represented by the general formula () or cyclopropane carboxylic acid enriched therein can be efficiently converted into a useful racemic form on an industrial scale. By combining this with the optical splitting method, it is also possible to convert it into a more useful (+) body.
The role it plays is extremely important. Furthermore, the racemate obtained by the method of the present invention is rich in the trans form, which is more effective as an ester, and the method of the present invention is advantageous in this respect as well. Next, the method of the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto. Reference example 1 In a 500ml flask, add 200g of toluene and (-)
-Trans- primary chrysanthemum chloride 27.8g, (-)-
25.0 g of trans-daisy chrysanthemum acid was charged, and 11.9 g of pyridine was added dropwise while stirring under a nitrogen atmosphere at 20 to 25° C., and stirring was continued for 5 hours. Then the reaction solution was diluted with 10
% hydrochloric acid, 5% caustic soda, and water, and concentrated to remove toluene. The residue was distilled under reduced pressure to form an acid anhydride with a boiling point of 130-135℃/0.2mmHg.
46.1g was obtained. . [α] _D −17.3° (C=1, CH ₂ Cl ₂ ) Reference example 2 55.5 g of levorotatory monochrysanthemum chloride and 50.0 g of levorotatory monochrysanthemum acid (both (+)-cis form: 3.3 %, (-)
-cis form: 19.8%, (+)-trans form: 11.7%,
(-)-trans form: has a composition of 65.2%. ) to synthesize the acid anhydride in the same manner as in Example 1, and the boiling point
90.6 g of acid anhydride with a temperature of 158-168°C/0.3 mmHg was obtained. Reference Example 3 In a 500 ml flask equipped with a distillation device, levorotatory chrysanthemum acid ((+)-cis form: 2.2%, (-)-cis form: 20.6%, (+)-trans form: 10.2%, ( −)
-Trans form: has a composition of 67.0%. ) and 275 g of acetic anhydride were charged, and the acetic acid produced was distilled off while heating. When the distillation temperature reaches 133°C, stop heating and heat under reduced pressure (0.3 to 0.4 mm
Hg) to obtain 104.8 g of acid anhydride. Example 1 In a 100 ml reaction vessel, 15.0 g of the (-)-dairyanhydride synthesized in Reference Example 1 and 35 g of toluene were placed in a nitrogen atmosphere, and 1.02 g of iodine was added thereto.
The mixture was stirred at 70°C for 60 minutes. The optical isomer ratio of the reactant was analyzed by gas chromatography as shown below, indicating that racemization had progressed. (+)-cis form: 5.4%, (-)-cis form: 4.3
%, (+)-trans form: 43.4%, (-)-trans form: 46.9% Next, toluene was concentrated and removed to obtain an acid anhydride as a residue. Furthermore, 20% caustic soda aqueous solution
25 g was added and stirred at 80° C. for 3 hours for hydrolysis. Toluene was added to the reaction solution to extract and remove impurities, and a 20% aqueous sulfuric acid solution was added for neutralization and acid precipitation. The precipitated oil was extracted with toluene, the toluene layer was washed with water, the toluene was concentrated and removed, and the residue was distilled to obtain 12.75 g of racemized carboxylic acid with a boiling point of 95-104°C/0.2 mmHg. It crystallized immediately and its melting point was 48-52°C. Moreover, the infrared absorption spectrum of this product matched that of (±)-daishu chrysanthemum acid. Example 2 In a 100 ml reaction vessel, 15.0 g of the levorotatory acid anhydride synthesized in Reference Example 2 and toluene were placed in a nitrogen atmosphere.
Add 35g, add 1.0g of iodine, and heat to 70℃.
The reaction was carried out in the same manner as in Example 1. During the reaction, a portion of the reaction solution was sampled at intervals, and the sample was chlorinated with thionyl chloride. The solution was analyzed by gas chromatography, and the results were as follows.

[Table] The reaction solution was concentrated to obtain an acid anhydride as a residue, which was hydrolyzed in the same manner as in Example 1. The melting point of the carboxylic acid was 48 to 52°C. Example 3 10.3 g of the levorotatory carboxylic acid anhydride synthesized in Reference Example 2 and 90 g of dioxane were placed in a 200 ml reaction vessel, 1.02 g of ferric chloride was added thereto, and the mixture was heated at 70°C.
Stirred for 60 minutes. The optical isomer ratio of the reactant was as follows, indicating that racemization had progressed. (+)-cis form: 3.1%, (-)-cis form: 3.4
%, (+)-trans form: 41.8%, (-)-trans form: 51.8% Next, a small amount of water was added to the reaction solution to decompose and remove ferric chloride, and then hydrolyzed in the same manner as in Example 1. 6.71 g of racemized carboxylic acid with a boiling point of 95-104°C/0.2 mmHg was obtained. Example 4 10.0 g of the levorotatory acid anhydride synthesized in Reference Example 3 and 90 g of toluene were placed in a 200 ml reaction vessel, and 1.67 g of tin tetrachloride was added thereto while cooling. This was then stirred at 50°C for 3 hours. When a part of this reaction product was collected and analyzed, its optical isomer ratio was (+)-cis: 1.3%, (-)-cis: 1.5%,
(+)-trans form: 43.1%, (-)-trans form: 54.1%. Example 5 20.0 g of the levorotatory acid anhydride synthesized in Reference Example 3 and toluene were placed in a 500 ml reaction vessel under a nitrogen atmosphere.
Prepare 180g and add 3.35g of aluminum chloride to this.
was added and stirred at 100°C for 7 hours. When a part of the reactant was collected and analyzed, (+)-cis form: 4.0%,
(-)-cis form: 6.7%, (+)-trans form:
40.5%, (-)-trans: 48.7%. Example 6 A 200 ml reaction vessel was charged with 10.0 g of the levorotatory acid anhydride synthesized in Reference Example 2 and 90 g of chloroform, 0.80 g of iodine was added thereto, and the mixture was stirred at 25°C for 3 hours. When a part of this reactant is collected and analyzed,
The optical isomer ratio is (+)-cis: 4.2%, (-)
-cis form: 1.6%, (+) -trans form: 26.9%,
(−)-Trans form: 67.3%. After continuing stirring at the same temperature for another 12 hours, the reaction product was analyzed and the optical isomer ratio was (+)-cis: 3.9%, (-)-cis: 3.8%, (+)-trans isomer. : 41.3%, (-)-trans form: 51.0%.

Claims (1)

[Claims] 1. General formula [In the formula, R ₁ and R ₂ each represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or an alkylene group having 3 to 5 carbon atoms by bonding R ₁ and R ₂ at the terminals. ] Racemize the optically active cyclopropanecarboxylic acid anhydride shown by reacting with a Lewis acid to obtain the acid anhydride, or hydrolyze it to obtain the carboxylic acid. A method for producing a racemized cyclopropanecarboxylic acid derivative, characterized by: 2 General formula [In the formula, R ₁ and R ₂ each represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or an alkylene group having 3 to 5 carbon atoms by bonding R ₁ and R ₂ at the terminals. ] Optically active cyclopropanecarboxylic acid represented by the general formula [In the formula, R ₁ and R ₂ have the same meanings as above. ] The optically active acid anhydride of cyclopropanecarboxylic acid shown by is derived, and this is racemized by reacting with a Lewis acid to obtain the anhydride, or this is then hydrolyzed to obtain the carboxylic acid. A method for producing a racemized cyclopropanecarboxylic acid derivative, the method comprising: obtaining a racemized cyclopropanecarboxylic acid derivative;